During the past two years we have initiated a program in polyene chemistry, which has been directly supported by NIH grant GM 40287. The accent associated with the work described is on the development of new methodology, based in large measure on vinylic organometallics, since coupling reactions of sp2 carbon centers bearing a metal tend to retain their stereochemical integrity. A number of polyene types were identified, including (1) conjugated, all E polyenes, containing between four and seven olefins, typified by the polyene macrolides. These natural products are potent, clinically useful antifungals; (2) doubly skipped polyenes, characteristic of the ubiquinones (CoQn). These coenzymes are valuable in vivo antioxidants. A third type of polyene, distinct from those above, is the biaryl nucleus. With each of these specific functional groups, novel reagents and/or technologies were envisioned which rely on either cuprate mediated transmetalations between vinylic stannanes or zirconocenes, or 'kinetic' higher order cuprate oxidations toward unsymmetrical biaryls. Lastly, new methodology for rapid construction of the prostanoid skeleton has been developed, the scope of which is to be examined. As an outgrowth of these projects, the discoveries made have expanded our involvement in organometallics to include (beyond Cu, Sn, and Zr) organozinc, palladium and nickel chemistry as they relate to polyenes as well. Thus, this renewal application will highlight our accomplishments relating to GM 40287, point out the important discoveries made along the way, and then focus attention, in large measure, on the new directions planned which rely on a variety of organometallic intermediates.